Chronic obstructive pulmonary disease (COPD), a representative lung disease, differs from asthma in that it is associated with irreversible airway obstruction. Currently, chronic obstructive pulmonary disease is a major cause of death in many countries; especially, it is predicted to be the third cause of death in humans in 2020 (Vestbo et al., 2013). COPD is a disease caused by pathologic changes of the bronchi and lung parenchyma due to inflammation in the airway and pulmonary parenchymal. COPD is characterized by bronchiolitis obliterans and emphysema (pulmonary parenchymal destruction), and it persistently inhibits and closes airflow in the lung tissue, eventually leading to death of a patient (Le et al., 2009). Types of chronic obstructive pulmonary disease include chronic obstructive bronchitis, chronic bronchiolitis, and emphysema. Such chronic obstructive pulmonary disease is caused by various causes such as cigarette smoke, dust, chemicals, air pollution, and bacterial infection (Li et al., 2012).
In particular, smoking is considered to be the major cause of chronic obstructive pulmonary disease, and over 80% of patients with actual chronic obstructive pulmonary disease are smokers (Rabe et al., 2007). Cigarette smoke contains a number of toxic chemicals, causing harmful changes in the lung tissue upon smoking (Stampfli and Anderson, 2009). These toxic chemicals cause infiltration of various inflammatory cells including neutrophils in the lung tissue, resulting in pulmonary inflammation (Terashima et al., 1997). Clinical studies have also shown a significant increase in the number of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) or sputum in patients with chronic obstructive pulmonary disease (O'Donnell et al., 2006). These inflammatory cells produce reactive oxygen species, inflammatory cytokines, chemokines, and a variety of enzymes that cause tissue damage (Profita et al., 2010). In particular, neutrophils play an important role in the development of chronic obstructive pulmonary disease (Hiemstra et al., 1998). Neutrophils not only produce many inflammatory cytokines, chemokines, and chemotactic factors, but also secrete elastinase, thereby destroying normal alveolar forms and eventually causing emphysema (Hoenderdos and Condliffe, 2013). Therefore, inhibition of infiltration of inflammatory cells, especially neutrophils, caused by cigarette smoke is recognized as an important therapeutic tool in the treatment of chronic obstructive pulmonary disease.
Airway mucus secretion is an innate immune response essential for the protection of airway mucosal surfaces from external pathogens (bacteria, viruses, and fungi) and stimuli (Voynow et al., 2009). However, excessive secretion and overproduction of airway mucus is a major pathophysiological feature of chronic obstructive pulmonary disease (COPD) (Rogers et al., 2006). Inhibition of excessive secretion and overproduction of airway mucus can be a primary strategy for the treatment of chronic obstructive pulmonary disease.
MUC5AC, one of the genes involved in the mucus secretion of mucin, is considered to be an important target factor because of the marked increase in its expression in COPD patients (Caramora et al., 2004). Expression of MUC5AC has been reported to be regulated by TNF-α, a major cytokine that causes COPD (Matera et al., 2010). Indeed, animal models with overexpression of TNF-α show pathological features of COPD, such as cell inflow into the lung, bronchial injury, and emphysema (Lundblad et al., 2005). Therefore, the expression and production of MUC5AC is an important factor for elucidating the mechanism of chronic obstructive pulmonary disease, and researches for preventing or treating this disease are actively conducted through a search of drugs inhibiting it.
Magnoliae flos is a word that refers to the buds of magnolia flowers belonging to Magnoliaceae, and the flower buds taste a little bit spicy. Magnolia is a tall deciduous tree cultivated nationwide for the purpose of gardening. Its flowers bloom earlier than leaves, and the flowering period is from March to April. Magnoliae flos is considered to be warm by nature in the oriental medicine. It is also regarded as effective for headache, back pain, and rhinitis, capable of treating sinusitis, and having a medicinal property as a painkiller.
Accordingly, the inventors of the present invention have studied a substance capable of treating chronic obstructive pulmonary disease by controlling the expression of MUC5AC induced by TNF-α and inhibiting neutrophil infiltration, selected a compound among the compounds separated from Magnoliae flos, which is effective for inhibiting the expression of MUC5AC, and confirmed that an extract of Magnoliae flos, a fraction or an active fraction obtained by fractionation thereof with an organic solvent, or a compound separated therefrom may be used to treat chronic obstructive pulmonary disease by inhibiting inflammatory cells, inhibiting the production of reactive oxygen species, and reducing cytokines in the bronchoalveolar lavage fluid of a chronic obstructive pulmonary disease mouse model, thereby completing the present invention.